• Media type: E-Article
  • Title: Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
  • Contributor: Riewald, Matthias; Petrovan, Ramona J.; Donner, Aaron; Mueller, Barbara M.; Ruf, Wolfram
  • imprint: American Association for the Advancement of Science (AAAS), 2002
  • Published in: Science
  • Language: English
  • DOI: 10.1126/science.1071699
  • ISSN: 0036-8075; 1095-9203
  • Origination:
  • Footnote:
  • Description: <jats:p>The coagulant and inflammatory exacerbation in sepsis is counterbalanced by the protective protein C (PC) pathway. Activated PC (APC) was shown to use the endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease activated receptor 1 (PAR1) on endothelial cells. Gene profiling demonstrated that PAR1 signaling could account for all APC-induced protective genes, including the immunomodulatory monocyte chemoattractant protein-1 (MCP-1), which was selectively induced by activation of PAR1, but not PAR2. Thus, the prototypical thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a role for this receptor cascade in protection from sepsis.</jats:p>